Solving opioid addiction remains elusive as ever as doctors rely on weaning those physically and psychologically dependant on the drugs through troubling substitutes such as methadone and buprenorphine, which can be addictive in their own right.
The lack of such a magic pill is readily apparent in the overflowing 12-step rooms and bodies piling up at the morgue from fatal overdoses.
But Laura Bohn at the Scripps Research Institute in Jupiter for decades took a different approach to saving these lives: Why not make a safer opioid, one that doesn’t result in death by depressing breathing? The loss of respiration is the cause of most accidental fatal opioid overdoses.
Last week, Bohn announced that she and her colleagues have indeed found such a Holy Grail, dubbed a biased opioid. Her finding, published in the scientific journal Cell on Nov. 16, outlines how the new opioid carries with it what amounts to a dimmer switch for the brain cells that control breathing and are affected by opioids.
“What we did was find a way to keep the pain centers on and prevent respiratory centers from engaging,” she said. “We’ve filed for a patent to protect the intellectual property but by publishing, we are giving the tools to the world. Anyone can make it.”
Bohn said the announcement of the new compound is a culmination of six years of work at Scripps and previous research going back to the 1990s. She shares the discovery of the new compound with Cullen Schmid, Thomas Bannister and other researchers at Scripps.
The National Institute on Drug Abuse, which financially supported the research, is thrilled with the discovery.
“We are pleased to have uncovered a potential new mechanism to create safer alternatives to opioid medications, ones that would be far less likely to cause the side effects that lead to overdose deaths associated with the misuse of opioids,” said NIDA Director Dr. Nora Volkow.
“We are excited that basic research on how opioid drugs work in the brain has led to this novel approach and that we continue to make critical progress in this area.”
Abuse of pills still high
Bohn calls her remarkable drug by an unremarkable name: SR-17018. It comes in the wake of President Donald Trump declaring a national emergency because of the opioid epidemic. It also comes out of Palm Beach County, which is well versed in the trail of death these drugs are leaving.
While illicit opioids are the primary concern with the rash of fatal overdoses, the abuse of prescription pills remains rampant and often serves as an on-ramp to heroin and illegal fentanyl. In Florida in 2016, at least 15 people died each day of opioid-related overdoses, according to new data released last week.
Palm Beach County remains the epicenter, leading all counties in heroin-related overdose fatalities with 571 souls lost in 2016. The Palm Beach Post published Heroin: Killer of A Generation, detailing the lives of all 216 people lost to the epidemic in the county in 2015.
New data by the Florida Medical Examiners Commission reported that prescription drugs associated with abuse — opiates, benzodiazepines, muscle relaxants, sleeping aids — continue to be found more often than illicit drugs in overdose victims.
Prescription drugs of one kind or another were responsible for the deaths of 3,550 people in Florida in 2016 — a 40 percent increase from the year before.
When told of Bohn’s discovery, Palm Beach County Medical Examiner Dr. Michael Bell, who deals with the bodies of overdose victims, remained skeptical. “I’ll believe it when I see it.”
And Bohn is clear that SR-171018 is not going to be available anytime soon. The next step is a series of trials to determine the toxicity and side effects, first in animals and then eventually with people.
“We’ve been working on it for a long time. I moved to Scripps to do this work,” she said.
What about the euphoria?
Bruce Goldberger, director of health forensic medicine at the University of Florida, said that Bohn’s work is encouraging, but he worries that the potential for abuse remains even if the threat of overdose is decreased. He said the real Holy Grail would be a pill that eliminates the respiratory risk and reduces pain but doesn’t produce the euphoria that addicts seek.
Currently, though, most of the work in the research field has been in the area of saving lives through accidental overdose — and that means keeping opioids from repressing respiration.
Researchers have been working hard in the past decade to make a safer opioid. And at least one drug company, Trevena, is seeking approval from the Food & Drug Administration for an opioid medication that touts reduced negative side effects, such as breathing suppression.
Professor Randy Blakely, executive director of the Brain Institute at Florida Atlantic University in Boca Raton, said these new opioids would be a much-needed new tool for doctors. An overdose-proof drug would save tens of thousands of lives annually, he said.
“It’s exciting that it’s at this stage,” Blackley said. “It’s pretty clear we need analgesics which treat severe pain (but) that don’t have a number of side effects.”
Working to solve addiction
Nearly 20 years ago, Bohn delved into how opioids attract an intracellular protein that is the culprit in respiratory arrest. The goal was to create an opioid that didn’t attract this protein. The new opioid is a drug that binds to the receptor in the brain so that it doesn’t engage with this protein.
Bohn said she is not done yet. She hopes to tackle other negative side effects of opioids, such as constipation, physical dependency and even addiction.
“It’s important to note that we haven’t solved addiction,” she said. “We are working on that and we are hoping to get a handle on it, but we think it is a huge advance to take away the threat of overdose.”
Blakely from FAU believes medical research can indeed arrest addiction one day, but it’s going to take a holistic approach that includes new opioids without side effects and the psychological approach currently used to treat individuals.
“It’s not just going to be a magic bullet,” he said. “But the brain and its synapses are incredibly complicated and those complications present opportunity.”